The inhibition of System N transporters lowers the protective effect by ALL-MSCs. (A,C) ALL-MSCs were transfected with scramble or SLC38A5-siRNA (see Materials and Methods). (A) The expression of SLC38A5 mRNA was evaluated after 4 ddays. Data are expressed as folds of the mean value obtained in untransfected MSCs, kept at 1, and are means ± SD of 5 independent experiments performed with ALL-MSCs derived from 3 distinct patients (UPN#6-7-16, supplemental Table 2A). **P < .01. (B) RS4;11 cells were treated with l-asparaginase in monoculture or coculture with scramble-transfected or SLC38A5-silenced ALL-MSCs, and the protection index was determined. Data are means ± SD of 3 independent experiments performed with ALL-MSCs derived from 3 distinct patients (UPN#6-7-16, supplemental Table 2A). *P < .05. (C) RS4;11 cells were treated with l-asparaginase in monoculture or coculture with ALL-MSCs in the absence or in the presence of L-Histidine (L-His, 10mM) or l-glutamic acid γ-monohydroxamate (GluγHA, 1mM). The protection index is shown in the 3 conditions. Data are means ± SD of 4 independent experiments performed with ALL-MSCs derived from 2 distinct patients (UPN#8-16, supplemental Table 2A). ***P < .001 vs the protection index obtained in the absence of inhibitors. For panels A, B, and C, in each panel different symbol identifies MSCs from an individual donor.